Project Summary For radiation therapy (RT), the capability to precisely define and delivery radiations with the targeted distribution and dose level and to adapt the treatment plan based on the tumor biological response to RT is the key for any successful clinical therapy and translational research. For improving the current RT protocols and develop new novel RT strategies, it is critical to conduct translational RT researches with the technologies and procedures analogous to those applied in clinical RT practice so that the research methods and results are clinically relevant and can be effectively translated to clinical studies and applications. The goal of this project is to establish practical and advanced PET/CT image-guided radiation therapy (IGRT) capability for translational RT researches. The significance and impact of this project are very clear: it will overcome a critical technical obstacle to transform the current practice of RT research that is almost solely relied on anatomic CT images to the one guided by functional images with the knowledge of actual tumor biological status and function. The success of this project is expected to have lasting impact to improving and accelerating the translational RT research and profound benefits to enhancing the cancer treatment. The research aims to develop an advanced animal PET and integrate it with an existing micro-CT/RT, evaluate and improve the performance through experiments of phantom imaging and system modeling, and conduct pilot animal studies to test the capability PET/CT image-guided translational radiation oncology applications. The newly developed PET detector technologies will be applied to overcome technical challenges to achieve high sensitivity (23%) and high, uniform resolution (1 mm) required by the quantitative imaging of small size tumor for RT studies. The novel imaging technology to be developed by this project should also be practical so that it can be adopted for other micro-CT/RT systems without fundamental technical difficulties.